Hyperphosphatemia is an electrolyte disturbance in which there is an abnormally elevated level of phosphate in the blood. Hyperphosphatemia can be caused by hypoparathyroidism due to the lack of PTH (parathyroid hormone), which has the effect of inhibiting renal reabsorption of phosphate. It is also commonly seen in chronic renal failure and caused by taking oral sodium phosphate solutions prescribed for bowel preparation for colonoscopy in children. Without effective treatment, hyperphosphatemia can lead to renal osteodystrophy, a collection of bone diseases characterized by bone pain, brittle bones, skeletal deformities and fractures.
The absorption of phosphate within the intestines has been investigated using in vivo triple lumen intestinal perfusion (Walton & Gray (1979) Clin. Sci. (Lond). 56(5):407-12). It has been found that phosphate is absorbed mostly in the jejunum, due not to pH differences, but to the larger pore size in its mucosa than in the ileum. The endogenous absorption of phosphate in the jejunal region via perfusion of phosphate-free solutions was found to be 20 μmol/30 minutes/40 cm. The transport of the phosphate occurs across the brush border of the jejunum via a sodium-phosphate co-transport system.
In a double-blind crossover study of 21 kidney failure patients receiving hemodialysis, it was shown that enteric-coated (targeted release in the small intestine) compared to gastric-coated (targeted release in acidic pH of the stomach) calcium carbonate allowed for higher doses without the possible risk of hypercalcemia (Ittel, et al. (1991) Klin. Wochenschr. 69(2):59-67). During the 6 month study, patients failed to develop hypercalcemia (defined as >2.75 mmol/l) when administered 3.1-3.6 g of enteric-coated CaCO3 phosphate binder per day, unlike during the administration of gastric-coated CaCO3.
Phosphate binders commercially available for treatment of hyperphosphatemia include PhosLo® (Calcium Acetate), Fosrenol® (Lanthanum Carbonate), and Renagel® (Sevelamer HCl). However, the inefficiency of commonly used phosphorus binders creates a clinical dilemma. The dose of the binder must be increased to control hyperphosphatemia, but increased risk of toxicity or other undesirable side affects of the binder results from the increased dose. This toxicity may include bone disease and aluminum dementia from aluminum-containing antacids and hypercalcemia and soft tissue calcification from calcium-containing antacids. These risks are particularly problematic in patients with chronic renal disease.